The role of E2F1-topoIIβ signaling in regulation of cell cycle exit and neuronal differentiation of human SH-SY5Y cells

Wang, Yanling; Zhao, Jing; Cao, Cuili; Yan, Yue; Chen, Jing; Feng, Fan; Zhou, Najing; Han, Shuo; Xu, Yanchao; Zhao, Juan; Yunli, Yan; Cui, Huixian

doi:10.1016/j.diff.2018.07.002

Cited by 9 publications

(8 citation statements)

References 45 publications

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“…Predicted peaks associated with each expression cluster were then further analyzed for known transcription factor motif enrichment, separately for cephalopod and ancient microsynteny (“Methods”, Supplementary Data 2 ). We find that the cephalopod microsynteny module 2, which is associated with multiple nervous tissues, was enriched for the transcription factors binding motifs Chop 26 , E2F1 27 , NeuroG2 28 , COUP-TFII 29 , Atf4 30 involved in nervous system differentiation and developmental transcription factors ZBTB18, Esrrb, Tcf21, Pitx1, GATA in all three developmental stages ( p < 1e−3). Module 4 was similarly enriched in transcription factor binding motifs involved in nervous system and general development such as Tcf3, TCFL2, GATA, Tcf21, and Pitx1 in all three developmental stages ( p < 1e−3).…”

Section: Resultsmentioning

confidence: 94%

Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization

et al. 2022

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Coleoid cephalopods (squid, cuttlefish, octopus) have the largest nervous system among invertebrates that together with many lineage-specific morphological traits enables complex behaviors. The genomic basis underlying these innovations remains unknown. Using comparative and functional genomics in the model squid Euprymna scolopes, we reveal the unique genomic, topological, and regulatory organization of cephalopod genomes. We show that coleoid cephalopod genomes have been extensively restructured compared to other animals, leading to the emergence of hundreds of tightly linked and evolutionary unique gene clusters (microsyntenies). Such novel microsyntenies correspond to topological compartments with a distinct regulatory structure and contribute to complex expression patterns. In particular, we identify a set of microsyntenies associated with cephalopod innovations (MACIs) broadly enriched in cephalopod nervous system expression. We posit that the emergence of MACIs was instrumental to cephalopod nervous system evolution and propose that microsyntenic profiling will be central to understanding cephalopod innovations.

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Section: Resultsmentioning

confidence: 94%

Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization

et al. 2022

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“…The activation of CBP/β-catenin is deemed the default active pathway in stem cells, which maintains an undifferentiated proliferative state [35,36]. For regular development to proceed, cells must exit the cell cycle and initiate the process of differentiation [37][38][39]. The array data analysis performed with GEO2R showed that the expression of CBP/β-catenin and its target genes of KLF4, MYC, and SOX2 were upregulated, generally synchronicity with the progression of cervical lesion grade.…”

Section: Discussionmentioning

confidence: 99%

Wnt3a/β-Catenin/CBP Activation in the Progression of Cervical Intraepithelial Neoplasia

Feng

Lin

Wang

et al. 2021

Pathol. Oncol. Res.

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Piwil2 reprograms HPV-infected reserve cells in the cervix into tumor-initiated cells (TICs) and upregulates Wnt3a expression sequentially, which leads to cervical intraepithelial neoplasia (CIN) and ultimately squamous cell carcinoma (SCC). However, little is known regarding Wnt signaling in the maintenance of TIC stemness during the progression of cervical lesions. We herein investigated the expression of canonical Wnt3a signaling and related genes by microarray data set analysis and immunohistochemical (IHC) staining of samples obtained by biopsy of normal cervix, low- and high-grade CIN, and invasive SCC tissue. Array data analyzed by GEO2R showed higher expression levels of Wnt signaling and their target genes, significant upregulation of stemness-associated markers, and notably downregulated cell differentiation markers in CIN and SCC tissues compared with those in the normal cervix tissue. Further, Gene Set Enrichment Analysis (GSEA) revealed that Wnt pathway-related genes significantly enriched in SCC. IHC staining showed gradually increased immunoreactivity score of Wnt3a and CBP and notable translocation of β-catenin from the membrane to the cytoplasm and nucleus during the lesion progression. The intensity and proportion of P16, Ki67 and CK17 staining also increased with the progression of cervical lesions, whereas minimal to negative Involucrin expression was observed in CIN2/3 and SCC. Therefore, canonical Wnt signaling may contribute to the progression of CIN to SCC and may be a potential therapeutic target.

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“…E2F1 signaling is well recognized and well-studied. Recent reports have shown that E2F1 can regulate a variety of biological processes, including the cell cycle, apoptosis, cell differentiation and DNA damage repair [28][29][30][31]. In addition, accumulating evidence shows that E2F1 signaling promotes tumorigenesis in different types of cancer, including lung cancer, breast cancer, prostate cancer and colorectal carcinoma.…”

Section: Discussionmentioning

confidence: 99%

TPX2 Promotes the Proliferation and Metastasis of Osteosarcoma Cells Through Stabilizing E2F1

Mao

Zhou

et al. 2021

Preprint

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Background: Osteosarcoma (OS) is the most common malignant bone cancer. Recently, more studies have shown that TPX2, a potential oncogene considered to be an important prognostic biomarker, is widely expressed in various tumors. However, until now, little is known about the impacts of TPX2 on the pathogenesis of OS.Methods: TPX2 expression of in OS cells and tissues was detected by Western blot and immunohistochemical analyses. Various assays were used to analyze OS cell proliferation and metastasis in vitro and in vivo. The effect of TPX2 on the expression of E2F1 and proteins encoded by E2F1-regulated genes was evaluated by Western blotting. Coimmunoprecipitation, immunofluorescence and in vitro ubiquitination assays were employed to explore the molecular mechanisms underlying the effect of TPX2 on stabilizing E2F1 and maintaining E2F1 signaling.Results: TPX2 is overexpressed in OS and is significantly correlated with the malignant progression of OS. TPX2 probably plays a critical role in the proliferation and metastasis of OS cells in vitro. Furthermore, TPX2 regulates E2F1 signaling by affecting the stability of E2F1, thereby affecting the proliferation and metastasis of OS cells. In addition, PSMD14 impacts the degradation and regulates the stability of E2F1. Most importantly, TPX2 regulates the interaction of E2F1 and PSMD14 to influence E2F1 degradation.Conclusions: Our research not only identifies TPX2 as a promising therapeutic target in cancer but also illuminates its underlying molecular mechanism. We showed that TPX2 promotes the malignant progression of OS by regulating E2F1 signaling.

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The role of E2F1-topoIIβ signaling in regulation of cell cycle exit and neuronal differentiation of human SH-SY5Y cells

Cited by 9 publications

References 45 publications

Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization

Emergence of novel cephalopod gene regulation and expression through large-scale genome reorganization

Wnt3a/β-Catenin/CBP Activation in the Progression of Cervical Intraepithelial Neoplasia

TPX2 Promotes the Proliferation and Metastasis of Osteosarcoma Cells Through Stabilizing E2F1

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